Snippets

Vantage Snippets are short summaries of breaking news stories.

Eyes return to the prize for Protagonist’s rusfertide

When the FDA halted all clinical work with Protagonist's rusfertide over cancer concerns, investors feared the worst. The lifting of that hold a mere three weeks later therefore prompted a similarly dramatic reaction: the stock surged 94% yesterday. But the shares still sit some 25% below levels seen before the clinical hold. Aside from requiring enhanced monitoring for skin cancer, the FDA seems comfortable for the programme to continue largely as before. Such a swift resolution is reassuring, though confidence in rusfertide’s potential has clearly taken a knock. More data will help, and two presentations before year end are now keenly awaited. The first is at the Liver Meeting, concerning a second indication for the project: hereditary haemochromatosis, a rare inherited disorder that causes iron build-up. Phlebotomy is the effective but burdensome standard of care. The abstract points to a dramatic reduction in phlebotomies as well as improvements in various pharmacological markers. The latest cut from an ongoing phase 2 trial in polycythemia vera is also due, possibly at Ash. Protagoinst confirmed yesterday that it still plans to start phase 3 in polycythemia vera early next year.  

Rusfertide (PTG-300) clinical programme in disorders of iron overload/excessive red blood cell production
Setting  Trial Next steps 
Polycythemia vera (rare chronic blood disorder that affects about 160,000 US patients) Phase 2 in phlebotomy-requiring PV Latest cut of data could be at Ash; previous presentation at EHA
Phase 2 in PV patients with elevated haematocrit Data could come 2022
Hereditary haemochromatosis (inherited iron overload blood disorder affecting over a million US people)  Open label phase 2 study fully recruited Data to be presented in oral session at AASLD November 13th
Third indication To be announced by YE 2021
Source: Company statements & clinicaltrials.gov. 

Astra’s Tackle disappoints

Astrazeneca is already seeking authorisation of its antibody combo AZD7442 for the prevention of Covid-19. Today’s topline data from the Tackle study show the project to have utility in the outpatient treatment setting, too, halving the risk of severe infection or death when given within seven days of symptom onset. In a prespecified subset who received the treatment within five days of symptom onset, AZD7442 cut this risk by 67% versus placebo. But there are a couple of reasons for caution. Most obviously, Merck & Co recently showed a similar level of efficacy in the same setting with molnupiravir, which has the vast advantage of being oral. And several other antibodies and antibody combos are already authorised for the treatment of non-hospitalised patients, with notably better headline efficacy than AZD7442. Perhaps ’7442 has a bit of an edge over these in that it is long-acting, and is delivered intramuscularly rather than needing to be infused – but molnupiravir clearly still wins on convenience. Forecast sales for ’7442 are far behind the blockbuster numbers the sellside has pencilled in for many of these treatments, and this situation seems unlikely to change on the back of the Tackle data. 

Selected Covid-19 MAbs and antivirals for outpatient treatment
Project Company Trial Cut in risk of hospitalisation/
death vs pbo
EUA for outpatient treatment?
AZD7442 Astrazeneca Tackle 50%*, "statistically significant" No
Molnupiravir Merck & Co Move-Out 50%, p=0.0012 Filed
BRII-196/BRII-198 Brii Biosciences Activ-2 78%, p<0.00001 Filed
Ronapreve
(casirivimab + imdevimab)
Regeneron/Roche COV-20678 70%, p=0.0024 Yes
Bamlanivimab + etesevimab Lilly Blaze-1 70%, p= 0.0004 Yes
Sotrovimab (VIR-7831) Glaxosmithkline/
Vir
Comet-Ice 79%, p<0.001 Yes
*Reduction in risk of severe Covid-19 or death. Source: company releases.

FDA seals Chemocentryx’s fate

Chemocentryx finally got the green light today for Tavneos in ANCA-associated vasculitis after a Pdufa delay, and the thumbs up follows previous precedent in that Pdufa date extensions rarely result in knockbacks. While the news sent Chemocentry’x shares soaring 64% the reaction is still not enough to put the company to levels seen before the mixed adcom in May, when shares lost three quarters of their value. The FDA’s concerns over liver toxicity seem to have been abated with the use of frequent liver function tests, and Tavneos's label comes without a black box warning. Tavneos, a complement C5a inhibitor, has been pegged as a pipeline in a product, but has suffered mid-stage setbacks in hidradenitis suppurativa and glomerulonephritis, thus leaving vasculitis as its main source of revenue.

Chemocentry'x pipeline
Product Mechanism of action Indication/status 2026e sales ($m)
Tavneos (avacopan) Complement factor C5a inhibitor Vasculitis (approved in US and Japan, EU decision by end of 2021) 610
Hidradenitis suppurativa (Aurora Ph2 failed), plan for Ph3 in severe patients 57
Glomerulonephritis (Accolade Ph2 failed), discussing path forward with FDA 41
Lupus nephritis study planned to start H1 2022 -
CCX140 CCR2 inhibitor Diabetic kidney disease (Ph2), development in focal segmental glomerulosclerosis discontinued -
CCX507 CCR9 inhibitor Ulcerative colitis (Ph1) -
CCX559 PD-L1 inhibitor Solid tumours (Ph1), oral -
CCX587 CCR6 inhibitor Th17-mediated inflammation (psoriasis; preclinical) -
Source: company releases & Evaluate Pharma.

Lattice miss is grating for Bristol Myers

Why deucravacitinib would fail in ulcerative colitis when it succeeded convincingly in psoriasis is not clear, but fail it has. In the phase 2 Lattice-UC study Bristol Myers Squibb’s oral Tyk2 inhibitor did not show improved clinical remission over placebo in moderate to severe UC. Neither did the trial meet its secondary efficacy endpoints. Deucravacitinib might still have a chance in the condition: a second phase 2 trial testing a higher dose is under way, and could report imminently. But hopes in UC will surely dim, not least because Pfizer has already discontinued its Tyk2, PF-06826647, in the disease. Perhaps deucravacitinib is a better bet in the various other disorders in which it is being trialled, though for now psoriasis remains the only indication for which analysts are forecasting sales – $2.4bn in 2026, according to Evaluate Pharma. The news will hardly help shore up confidence in Bristol’s biggest pipeline hope, which has already been dented by regulatory concerns. The company’s shares have slid heavily since the FDA slapped surprisingly stringent warnings on the related Jak-inhibitor class, with investors fearful that the regulator might consider the Tyk2 mechanism to carry similar risks.

Selected clinical-stage projects targeting Tyk2
Project Company Status Trial details
Deucravacitinib
(BMS-986165)
Bristol Myers Squibb Psoriasis (ph3) Poetyk-PSO-1 (NCT03624127) and Poetyk-PSO-2 (NCT03611751) hit
Psoriatic arthritis (ph3) NCT04908202 and NCT04908189, end 2023
Ulcerative colitis (ph2) Lattice-UC (NCT03934216) failed; IM011-127 (NCT04613518) ends 2021
Crohn's disease (ph2) NCT03599622, ends 2023
Lupus nephritis (ph2) NCT03943147, ends 2023
Systemic lupus erythematosus (ph2) NCT03920267, ends 2023
PF-06826647 Pfizer Psoriasis (ph2) NCT03895372, completed by no results reported
Hidradenitis suppurativa (ph2) NCT04092452, ends 2022 (includes brepocitinib & PF-06650833 arms)
Topical brepocitinib
(PF-06700841)*
Pfizer Atopic dermatitis (ph2) NCT03903822, hit Mar 2021
Psoriasis (ph2) NCT03850483, ends 2021
Oral brepocitinib
(PF-06700841)*
Pfizer Psoriatic arthritis (ph2) NCT03963401, completed but no results reported
Systemic lupus erythematosus (ph2) NCT03845517, ends 2022
Hidradenitis suppurativa (ph2) NCT04092452, ends 2022 (also includes PF-06826647 & PF-06650833 arms)
Vitiligo (ph2) NCT03715829, completed, no results (also includes ritlecitinib (PF-06651600) arm)
Crohn's disease (ph2) NCT03395184, ends 2022 (also includes ritlecitinib (PF-06651600) arm)
NDI-034858 Nimbus^ Plaque psoriasis (Ph2) NCT04999839, ends 2022
OST-122** Oncostellae Ulcerative colitis (ph1/2) NCT04353791, ends 2022
ICP-332 Innocare Ph1 in healthy volunteers Trial begun in China
BMS-986322 Bristol Myers Squibb Ph1 in healthy volunteers NCT04175925, recruitment on hold owing to Covid-19
Notes: *also hits Jak1; **also hits Jak3 & ARK5; ^Bristol Myers Squibb has option via Celgene acquisition. Sources: Evaluate Pharma, clinicaltrials.gov.

Another billion-dollar tuck-in for Boston

Boston Scientific’s management has spoken in doom-laden tones of the effect Delta variant Covid-19 is having on elective procedures, and has hinted to analysts that it might not meet its third-quarter sales growth forecast of 12-14% as a result. Its acquisition of the Canadian group Baylis Medical Company for $1.75bn cash today is therefore a way of guarding against, or at least making up for, a revenue shortfall. Baylis is squarely in Boston’s cardiovascular wheelhouse as a manufacturer of minimally invasive products to aid in procedures like cardiac ablation, left atrial appendage closure and mitral valve intervention. It is growing at double-digit rates, Boston says, and is expected to generate revenues approaching $200m next year. The purchase of Baylis is Boston’s third $1bn-plus deal this year – notable given that the group has only done nine such deals in the past quarter century. And more might be on the way; Boston has repeatedly stated its intention of growing through acquisitions. At the end of June Boston had $2.7bn cash on hand, and investors might now be starting to wonder how deep its pockets are. 

Boston's $1bn-plus deals of the last 25 years
Date Target Value ($bn) Focus Vantage coverage
Oct 2021 Baylis Medical Company  1.8 Cardiology -
Sep 2021 Surgical business of Lumenis 1.1 Surgery; general hospital & healthcare supply Boston Scientific’s next move
Jan 2021 Preventice Solutions 1.2 Cardiology; patient monitoring Boston adds to furious deal-making pace
Aug 2019 BTG 4.2 Cardiology; surgery; neurology; radiology Boston bid for BTG shows dreams can come true
Aug 2015 Men's Health business of American Medical Systems 1.7 Urology Endo exits medtech – almost
Jun 2012 Cameron Health 1.4 Cardiology Boston Scientific remakes itself to face the future
Apr 2006 Guidant 27.0 Cardiology; radiology -
Sep 1998 Schneider 2.1 Cardiology -
Apr 1997 Target Therapeutics 1.1 Cardiology; neurology -
Source: Evaluate Medtech.

Astrazeneca tries its luck in Covid-19 prevention

Astrazeneca’s filing for emergency use of AZD7442 for Covid-19 prevention looks like an attempt to steal a march on Regeneron and Lilly’s already authorised MAbs. Whether it will succeed is a separate question. Astra says “AZD7442 (could) be the first long-acting MAb to receive an EUA for Covid-19 prevention”, though Regeneron’s Regen-Cov and Lilly’s bamlanivimab/etesevimab, both normal-acting, already have EUAs for post-exposure prophylaxis in subjects at high risk of severe Covid-19. Astra’s application appears to seek a broad EUA for Covid-19 prevention, even though only its pre-exposure study, Provent, succeeded; Storm Chaser, for post-exposure prophylaxis, failed. A separate question for the FDA will be whether to authorise AZD7442 in vaccinated as well as unvaccinated people; the Regeneron and Lilly prophylaxis EUAs are for unvaccinated people and those who are vaccinated but unable to mount a strong immune response, but Astra’s trials were specifically in the unvaccinated population. A similar consideration exists for Merck & Co’s oral antiviral molnupiravir, which last week scored in a Covid-19 treatment study in unvaccinated people. While it might seem unethical to deny a drug based on patients’ vaccination status, reimbursement for molnupiravir might be justifiable only in its specific studied population.

Selected antivirals & MAbs for treating Covid-19 
Project  Company  Setting  Trial Vaccinated people allowed?
Molnupiravir Merck & Co/Ridgeback  Outpatient treatment Move-Out, succeeded No*
Post-exposure prophylaxis Move-Ahead, data H1 2022 No
AT-527 Roche/Atea Outpatient treatment Morningsky, ends Nov 2021 Yes if vaccinated >40 days previously
PF-07321332 Pfizer Low-risk outpatient treatment NCT05011513, ends Oct 2021 No, except those with underlying condition
High-risk outpatient treatment NCT04960202, ends Nov 2021 No
Post-exposure prophylaxis NCT05047601, data H1 2022  No
Favipiravir Appili Outpatient treatment Preseco, ends Sep 2021 Yes
RHB-107 (upamostat) Redhill Biopharma Outpatient NCT04723537, ends Sep 2022 Yes
AZD7442  Astrazeneca Post-exposure prophylaxis Storm Chaser, failed No
Pre-exposure prophylaxis Provent, succeeded No
Outpatient treatment Tackle, data H2 2021 No
Regen-Cov (casirivimab + imdevimab) Regeneron Treatment (has EUA) COV-20678 No
Post-exposure prophylaxis (has EUA**) COV-2069 Yes
Bamlanivimab + etesevimab Lilly/Abcellera Treatment (has EUA) Blaze-4 Yes, except low-risk individuals
Post-exposure prophylaxis (has EUA**) Blaze-2, part 1 No
Source: Evaluate Pharma & clinicaltrials.gov. Notes: *per Wolfe Research, not specified on clinicaltrials.gov; **in unvaccinated people, or vaccinated people unable to mount strong immune response.

Vedanta makes Clostridioides difficile look easy

Microbiome-targeting agents seem to have a decent shot at treating C difficile infections, if they are rather less certain in other settings. Vedanta said today that its pill VE303, a combination of eight strains of live bacteria grown in cell banks, achieved a 31.7 percentage point risk reduction versus placebo in the rate of infection recurrence. The data refer to only the higher dose administered in the phase 2 Consortium trial; on the lower dose Vedanta is silent. Still, the data were good enough to spur Barda to hand over $23.8m to support phase 3 studies, under a contract it has had with Vedanta since last year. These trials ought to begin next year, putting Vedanta some way behind Seres and Ferring. The former hopes to file its C diff project SER-109 for US approval next year, and Ferring should get its pivotal data in the same time frame. Elsewhere, Kaleido Biosciences reported topline biomarker data from a tiny trial of its microbiome asset KB295 in mild-to-moderate ulcerative colitis. A phase 2 trial is slated for 2022, and the group will hope to avoid the dismal fate of Seres in this disease

Data from the Consortium trial of Vedanta's VE303
  High-dose VE303 Placebo
Recurrence rate within 8wk 13.8% 45.5%
Reduction vs placebo in the odds of a recurrence 81%, p=0.0077
Source: company release.

Health tech Spacmania flags

The medtech Spac scene seems to be going through one of its periodic lulls, with just one deal announced in August and one in September. The latter is the acquisition of Prenetics, a genomics and diagnostics testing company based in Hong Kong, by the Nasdaq-listed Artisan Acquisition Corp. The deal values Prenetics at around $1.3bn, not unreasonable considering its forecast 2021 revenues of $205m. Once public the group, whose claim to fame is supplying the Covid-19 tests used by the UK’s Premier League, has ambitions to expand into the US via M&A. Looking at the other end of the Spac process, seven companies have closed their deals and now enjoy stock market listings. But their performance has been decidedly mixed. Vicarious Surgical’s 50% rise reflects the high hopes for new entrants into the fast growing robotic surgical space, whereas the baby-monitoring tech company Owlet crashed 26% on August 25 when several of its backers, including its Spac’s sponsor, Sandbridge Capital, registered to sell their shares. 

Health tech Spac deals announced in Q3
Target Spac (main backer)  Focus Date announced
Prenetics  Artisan Acquisition (Artisan) Diagnostics and genomics Sep 15
Memic Innovative Surgery Medtech Acquisition Corp (Medtech Acquisition Sponsor) Robotic surgery Aug 13
Gelesis Capstar Special Purpose Acquisition Corp (Capstar Partners and Pimco) Gastrointestinal Jul 19
Heartflow Longview Acquisition Corp II (Glenview Capital Management) Cardiovascular Jul 15
Hyperfine and Liminal Sciences Healthcor Catalio Acquisition Corp (Healthcor Management and Catalio Capital Management) Imaging/patient monitoring Jul 8
Source: company releases.

 

Health tech Spac deals closed in Q3
Target Spac (main backer)  Focus Closing date Share price change*
LumiraDx CA Healthcare Acquisition Corp (Covington Associates and Pleasant Bay Capital Partners) Diagnostics Sep 28 (9%)
Vicarious Surgical D8 Holdings Corp
(D8 Sponsor)
Robotic surgery Sep 20 50%
Somalogic  CM Life Sciences II (Casdin Capital and Corvex Management) Proteomics Sep 1 24%
Humacyte Alpha Healthcare Acquisition Corp (AHAC Sponsor) Bioengineered vascular grafts Aug 26 16%
Sema4 CM Life Sciences (Casdin Capital and Corvex Management) Genomics Jul 23 (24%)
Owlet  Sandbridge Acquisition Corp (Sandbridge Capital and Pimco) Digital health  Jul 16 (44%)
Sharecare Falcon Capital Acquisition Corp (Falcon Equity Investors) Telehealth Jul 2 (18%)
*Share price change calculated from $10, the price at which Spacs IPO, to July 30. Source: company releases.     

Xenon finally finds a way forward with epilepsy win

Seven years after floating Xenon could finally have found a winner. Highly encouraging data from the phase 2b X-Tole trial of XEN1101 sent shares in the company to a record high. The study tested the Kv7 potassium channel modulator in adults with focal epilepsy; XEN1101 significantly reduced seizure frequency versus placebo across three doses, and hit secondary measures. This was a highly refractory patient group that had failed a median of six previous anti-seizure medications; half remained on three background ASMs. On a call Xenon executives said it was highly unlikely to win approval on this trial alone, but hoped that regulators would accept X-Tole as one of two required studies. Safety also looked encouraging, with no suggestion that XEN1101 was worsening mood; many ASMs have a black box warning of suicidal ideation. Stifel analysts said the data beat expectations and looked in line with the recently approved Xcopri. To put a value on the opportunity, Angelini agreed to pay almost $1bn earlier this year for Arvelle, owner of Xcopri's European rights. Analysts expect Xcopri's sales in the US, where it is sold by SK Biopharmaceuticals, to reach $846m by 2026, according to Evaluate Pharma.

Source: Xenon investor presentation.

US FDA approval tracker: September

While there were FDA setbacks for Calliditas and Verrica last month there were also a couple of early oncology approvals. One such win was for Tivdak, Seagen/Genmab’s treatment for recurrent or metastatic cervical cancer. However, expected sales of Tivdak could be hit by an unexpected black box warning regarding ocular toxicity. An early approval for Takeda’s Exkivity also came with safety implications. The oral therapy, used to treat lung cancer driven by EGFR exon 20 insertions, has a black box warning for QTc prolongation. J&J’s competing project Rybrevant does not come with a warning, but is less convenient as it is an infused antibody. Separately, Takeda investors are still holding out for FDA news on Eohilia after the FDA's action date was missed in April. Takeda says Eohilia could become the first treatment for eosinophilia oesophagitis, but with a filing for Sanofi/Regeneron’s Dupixent expected next year Takeda will want the regulators to hurry.

Notable first-time US approval decisions in September
Project Company Indication(s) 2026e sales by indication ($m) Outcome
Qulipta
(atogepant)
Abbvie Episodic migraine prevention 954 Approved
Tivdak (tisotumab vedotin) Seagen/Genmab Previously treated recurrent or metastatic cervical cancer 629* Accelerated approval (over 2 weeks early)
Nefecon Calliditas IgA nephropathy  629** Extended to Dec 15
Exkivity (moborcertinib) Takeda EGFR exon 20 Insertion+ NSCLC 436 Accelerated approved (over a month early)
Livmarli
(maralixibat)
Mirum Cholestatic pruritus in Alagille syndrome 432 Approved
VP-102 Verrica Molluscum contagiosum 271* Second CRL
(deficiencies at contract manufacturer)
Eohilia
(TAK-721)
Takeda Eosinophilic esophagitis 187 No decision yet (April Pdufa missed)
Illuccix Telix Prostate cancer imaging 42 Extended to December 23
Reltecimod Atox Bio Resolution of organ dysfunction in necrotising soft tissue infections - Supposed to have been Sep 30, no news released
Epsolay Sol-Gel Papulopustular rosacea - No decision yet (delayed in Apr)
*Sales by indication not split out, **includes undisclosed partner sales. Source: Evaluate Pharma & company releases
 
 
Supplementary and other notable approval decisions in September
Product Company Indication (clinical trial) Outcome
AVT02
(Humira biosimilar)
Alvotech/Teva Inflammatory conditions, PK study AVT02-GL-101, efficacy study AVT02-GL-301 Delayed
(facility inspection)
Repatha Amgen Paediatric patients with heterozygous familial hypercholesterolemia (Hauser-RCT) Approved
Invega Hafyera (Paliperidone palmitate 6-month, PP6M) J&J Adults with schizophrenia (Route 6) Approved
INP104/
Trudhesa
Impel 505(b)(2) application acute treatment of migraine (dihydroergotamine mesylate with olfactory delivery) Approved
Brukinsa Beigene Marginal zone lymphoma who have received at least one prior anti-CD20-based therapy (Magnolia, Ph1/2) Approved
Brukinsa Beigene Waldenström’s macroglobulinemia (Aspen) Approved
Opzelura (ruxolitinib cream) Incyte Atopic dermatitis (TruE-AD1, TruE-AD2 Approved
Jakafi Incyte/Novartis Paediatric patients with steroid-refractory GvHD (Reach3) Approved
Byooviz
(Lucentis biosimilar)
Biogen/
Samsung Bioepis
Wet AMD, myopic choroidal neovascularisation and macular oedema following retinal vein occlusion Approved
Erbitux + Braftovi Lilly/Pfizer Adult patients with metastatic colorectal cancer with a BRAF V600E mutation (Beacon CRC) Approved
Source: Evaluate Pharma, company releases & clinicaltrials.gov